In a concurrent patent application (BFA 12/95) "Method for controlling the ion generation rate for the mass selective loading of ions in ion traps" the same subject is addressed as in this patent application. The descriptive text of the referenced patent application is therefore to be deemed included in full here.
For some purposes it is desirable to resonantly excite the oscillations of ion species of several different mass-to-charge ratios in ion traps simultaneously but to leave other ion species unexcited. For example, one can remove undesired ions from the trap by such resonant excitation and retain only ions of desired mass-to-charge ratios in the ion trap. Or one can supply ions of several mass-to-charge ratios with oscillation energy simultaneously in order to start reactions with other gas molecules or to induce self-decomposition by collisions with collision gas molecules.
A particularly important application is the mass selective loading process of ions of one or more specified m/z ratios in the ion trap. The intention is to eject undesired ions from the trap during the loading procedure to be able to fully utilize the limited storage capacity of the trap for the desired ions.
A special case of mass selective loading with simultaneous reactions of the ions involves the method of chemical ionization (CI) with selection of reaction paths, as described for example in DE 4 324 233 (Franzen and Gabling, U.S. application Ser. No. 08/277,666).
The loading of ions can be performed either by generating ions inside the trap, e.g. by injecting electrons and simultaneously introducing substance vapors, or by generating ions outside the trap and transferring them to the trap by ion-optical means.
As is known from U.S. Pat. No. 4,761,545 (Marshall, Ricca, and Wang), one can resonantly excite the oscillations of different ion species roughly simultaneously by applying mixtures of discrete frequencies to certain electrodes of the ion traps. This is possible both for magnetic ion traps (called Penning ion traps, or ion-cyclotron resonance ion traps, ICR) and for RF quadrupole ion traps (called Paul ion traps). In the patent, the frequency mixture is calculated digitally, stored digitally, and then output to at least one electrode of the ion trap via suitable digital-to-analog converters and output voltage amplifiers. The desired frequency mixture waveform in the time domaine is calculated by inverse Fourier transformation from a specified frequency profile in the frequency domaine, whereby the frequency profile contains the oscillation frequencies of the undesired ions and excludes the oscillation frequencies of desired ions as gaps in the profile. To keep the required dynamic range for the frequency mixture amplitude values small, the phases of the discrete frequencies are shifted, from frequency to frequency, in a nonlinear but smooth function. A quadratic function of the frequency is especially recommended by Marshall et al. From a set of frequency values with amplitudes and phases in the frequency domaine, a sequence of amplitude values is generated by inverse Fourier transformation in the time domain for a waveform period. The number of amplitude values in the time domaine, and thus the duration of the waveform interval, corresponds to the number of frequency values in the frequency domaine. This method has become well-known under the acronym "SWIFT" (Stored Waveform by Inverse Fourier Transformation") in the field of ICR mass spectrometry. As described in the patent, the frequency mixture of the waveform interval is very specifically tailored, by so-called apodization, to a one-time output to the ion trap. Naturally, it can be output a number of times in succession.
However, if the SWIFT method as recommended by Marshal et al. is used for multiple subsequent output processes over long times, considerable drawbacks appear. In a single waveform interval as generated by inverse Fourier transformation, it chiefly generates a fast frequency sweep of short duration. The excitation starts at low frequencies, then passes through the series of individual frequencies essentially one after the other, and finally ends at high frequencies by decreasing the amplitudes (see FIG. 2). Consequently, an ion is only accelerated during a very short time span within the waveform interval as a whole--for the rest of the time its excitation is practically nonexistent. This behavior is generated by the nonlinear phase shift, particularly by the quadratic relationship with frequency. The frequency function in the time domaine is proportional to the derivative of the phase function in the frequency domaine so the quadratic phase shift referred to as optimal generates a linear frequency sweep. If output of the waveform period signal is repeated a number of times in succession, a sequence of short excitation pulses is imparted on an ion of given mass at the repetition rate of the waveform intervals, and in between the excitation pulses practically nothing happens to the ion. Since it is desirable to have continuous ejection of the ions during ion generation in order to avoid overloading the ion trap, this method is inadequate for the present purpose, despite its great merits in ICR mass spectrometry.
In EP 362 432 A1 (Franzen and Gabling) a digitally generated "broadband signal" was proposed for this purpose, which constitutes a mixture of discrete, continuously present frequencies. However, this document did not provide any information how the mixture of frequencies can be calculated and can be made matching the requirements of limited dynamic ranges of amplitudes and voltages, as it is necessary both for digital presentation and for further electronic processing in output amplifiers.
In U.S. Pat. No. 5,324,939 (Louris and Taylor) the method proposed by Marshall, Ricca and Wang is optimized by critical selection of the proportionality factor between the phase and square of the frequency, and by structuring the amplitudes of adjacent frequencies like a comb so that a fairly uniform presence of all the frequencies is said to be achieved. According to the figure in the patent the method provides a frequency range which begins and ends at zero and in between generates a broadband signal with a very favorable shape.
Since this patent is the closest state of the art, a critical review should be appropriate. The following phase relationship is preferred by Marshall et al., and also used by Louris and Taylor: EQU Phase=2 .pi.p frequency.sup.2 /n,
whereby n is the number of amplitude values in the waveform interval and p is a proportionality factor. The proportionality factor p will be referred to in the following as "phase factor".
If p=1, one obtains the case of a short linear frequency sweep, whereby the frequency sweep just covers the full waveform interval once (see FIG. 2). This case was regarded by Marshall, Ricca and Wang as optimal for their purposes.
If p=1/2, the frequency sweep covers only the first half of the waveform period, and the second half is vacant. If p=2, the frequency sweep is extended in length to double the length of the waveform interval and is pulled, in two cycles, over the waveform interval twice. The first half of the frequency sweep and the second half are superimposed. The sweep alternates between frequencies of the first and those of the second half. However, each frequency is still only output once per waveform interval in a very short time span. With larger p factors the frequency sweep is pulled over the waveform period cyclically p times (see FIG. 3 for p=11). Here too each frequency is output only once per interval within a very short time span.
If p=0, n, 2n, 3n, . . . the frequency sweep is distorted to form a single point because all the cosine functions of the frequency mixture have the same phase and all the amplitudes are superimposed at the beginning of the waveform interval. In the rest of the waveform interval, the frequency amplitudes disappear by interference. If p forms a non-simplifyable fraction r/s of the number n, that is, p=(r/s)n, r and s being integers, the frequency sweep degenerates at s or s/2 points (depending on whether s is odd or even), which are uniformly distributed over the waveform period.
By trying out large values for p it looks as if it were possible to obtain a uniform distribution of frequencies over the waveform period. In reality there are only numerous types of beat. Very slight changes in the phase factor p sometimes cause dramatic changes in the structure of the frequency mixture. Nevertheless, each frequency is only output once per waveform period in a very short time span. Only the sequence in the output of the different frequencies is mixed.
If p=(3n+1)/8, for example, it is possible to generate four frequency sweeps which take place one after the other in the waveform period, whereby each of the four frequency sweeps contains only one frequency in four.
Louris and Taylor now teach us in U.S. Pat. No. 5,324,939 that the uniformity of the presence of the frequencies over the waveform period could be proved by dividing the waveform period into two halves and subjecting the values of both halves to Fourier analysis. If p=1, it is impressive to see that the first half of the interval contains only the low frequencies whilst the second one contains the high frequencies (see FIG. 2). However, this type of investigation does not constitute proof. Repeating the frequency sweep four times as described above with p=3(n+1)/8 naturally means that both the first half and the second half apparently contain the full range of frequencies. Even the quarters seem to contain all frequencies. Because the waveform interval now is divided into four and the quarters are subjected to Fourier analysis the distribution of frequencies seems to be uniform (see FIG. 4). However, since the Fourier analyses become coarser due to the smaller number of points in the quarter intervals and one now only analyzes one frequency in four, the conclusions by Louris and Taylor are incorrect.
Furthermore, Louris and Taylor propose a comb structure of frequencies. The sharpest comb structure as suggested by Louris and Taylor involves applying a finite amplitude to only one frequency in two and omitting the frequencies in between. If one generates a waveform period from such a frequency structure by inverse Fourier transformation, the value sequences are automatically identical to the waveform period in the first and second halves. Since only half the frequencies are included, only half the quantity of values are necessary for describing them. If one now subjects the two halves of the value sequence to Fourier analysis, both halves must manifest the same frequency range (see FIG. 5). However, this does not constitute evidence that the presence of frequencies is uniform. The test method of Louris and Taylor for uniform presence of frequencies throughout the waveform period is only of very limited use although better test methods cannot be suggested here. For this reason, critical analysis is necessary every time this test method is applied.
The patent of Louris and Taylor also erroneously states, that the random selection of phases does not produce uniform a presence of frequencies.
In U.S. Pat. No. 5,314,286 (Kelley) a method is described which uses electronic noise for the purpose of ion excitation. By filtering out certain frequencies it is possible to leave ions of selected mass-to-charge ratios unexcited by filtering out their resonant frequencies from the noise. This method is much better suited to the above-mentioned purposes of mass selective loading of ions because in principle all the frequencies are continuously present over the entire time of noise, disregarding statistical fluctuations of the individual frequency amplitudes according to frequency and time. However, the patent provides no information about the definition or generation of noise.
PCT/US93/07 092 A1 (Kelley) describes a method of digitally generating the electronic noise in accordance with U.S. Pat. No. 5,134,286 by adding discrete sine-waves, although the concept of noise is restricted to frequencies with the same amplitudes. By gradually optimizing the phases of the discrete frequencies, a noise signal is generated which has a small dynamic range of amplitudes. For each frequency to be added there is a trial procedure as to which phase produces the smallest enlargement of dynamic range. Filtering can be generated by omitting the relevant frequencies during addition. The patent tells nothing about the length of the waveform interval or the addition of the sine-wave oscillations or about the possibility of creating a repeatable waveform interval. The waveform interval calculated has to have the same length as the time for which noise is to be applied to the ion trap electrodes. For an ionization cycle of 1,000 milliseconds and an output rate of 10 megahertz, which was specified for an adequately high oversampling rate for a commercially available instrument based on this patent, a very fast electronic memory is required with a capacity of 20 megabytes.
This method has the disadvantage that the arithmetic process of generating the frequency mixture is highly elaborate. Both the time interval necessary for the frequency mixture and the calculation method contribute to computation time.
There is, however, a special method for the generation of an alternating electric field with a mixture of frequencies from a digital value sequence according to DE 4 316 737 (Franzen, Gabling, and Heinen) which reduces memory requirement for the above example to 2 megabytes. Benefitting from the fact that the side band structures of the Mathieu equation agree with those of the digital frequency generation, oversampling can be dispensed. If the Mathieu side band oscillations of the ions in the RF ion trap match the side bands of the digital frequency generation the motion of the ions is not undesirably disturbed. The method reduces not only the memory requirement for storing the waveform but also the computation requirement, and requirements for the speed of the D/A converters.